Although in itself neither degenerative nor fatal, the chronic pain of fibromyalgia is pervasive and persistent. Most people with fibromyalgia report that their symptoms do not improve over time. An evaluation of 332 consecutive new people with fibromyalgia found that disease-related factors such as pain and psychological factors such as work status, helplessness, education, and coping ability had an independent and significant relationship to FM symptom severity and function.

A mode of inheritance is currently unknown, but it is most probably polygenic. Research has also demonstrated that fibromyalgia is potentially associated with polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems. However, these polymorphisms are not specific for fibromyalgia and are associated with a variety of allied disorders (e.g. chronic fatigue syndrome, irritable bowel syndrome) and with depression. Individuals with the 5-HT2A receptor 102T/C polymorphism have been found to be at increased risk of developing fibromyalgia.

All ethnic groups and income levels are susceptible to the illness. The CDC states that CFS is "at least as common" in African Americans and Hispanics as Caucasians. A 2009 meta-analysis, however, showed that compared with the White American majority, African Americans and Native Americans have a higher risk of CFS, though it acknowledged that studies and data were limited. More women than men get CFS — between 60 and 85% of cases are women; however, there is some indication that the prevalence among men is underreported. The illness is reported to occur more frequently in persons between the ages of 40 and 59. CFS is less prevalent among children and adolescents than among adults.

Blood relatives of those who have CFS appear to be more predisposed. There is no direct evidence that CFS is contagious.

Psychological stress, childhood trauma, perfectionist personalities, old age, lower middle education, low physical fitness, preexisting psychological illness, and allergies may be risk factors for developing chronic fatigue syndrome. This has led some to believe that stress-related visceral responses underlie CFS. Pre-existing depressive and anxiety disorders, as well as high expectation of parents and family history were predisposing factors identified in another review.

People with CFS and their relatives tend to attribute their illness to physical causes (such as a virus or pollution) rather than to psychological causes. Such attributions are associated with increased symptoms and impairment, and worse outcomes over time.

A systematic review described improvement and occupational outcomes of people with CFS found that "the median full recovery rate was 5% (range 0–31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8–63%). Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome." ... "In five studies, a worsening of symptoms during the period of follow-up was reported in between 5 and 20% of patients." A good outcome was associated with less fatigue severity at baseline. Other factors were occasionally, but not consistently, related to outcome, including age at onset (5 of 16 studies), and attributing illness to a psychological cause and/or having a sense of control over symptoms (4 of 16 studies). Another review found that children have a better prognosis than adults, with 54–94% having recovered by follow-up compared to less than 10% of adults returning to pre-illness levels of functioning.

Functional somatic syndromes may occur in 6 to 36% of the population.

The most common causes of myalgia by injury are: sprains and strains.

Genetic differences relating to toxicant metabolism pathways, such as polymorphisms and differences in expression in CYP2D6, NAT2, GSTM1, and PON1 and PON2, have been proposed as a cause for differences in susceptibility to MCS. Elevated nitric oxide and peroxynitrite (NO/ONOO-) could then cause the symptoms of MCS and several related conditions, including fibromyalgia, posttraumatic stress disorder, Gulf War syndrome, and chronic fatigue syndrome.

Sudden cessation of high-dose corticosteroids, opioids, barbiturates, benzodiazepines, caffeine or alcohol can induce myalgia in many respects.

Psychological trauma or stress appears to predispose persons to a functional somatic syndrome. HPA axis, autonomic nervous system, and immune response to stress has been proposed as a mediating mechanism. Upper airway resistance syndrome may also be implicated.

While risk factors vary with age and gender, most of the common chronic diseases in the US are caused by dietary, lifestyle and metabolic risk factors that are also responsible for the resulting mortality. Therefore, these conditions might be prevented by behavioral changes, such as quitting smoking, adopting a healthy diet, and increasing physical activity. Social determinants are important risk factors for chronic diseases. Social factors, e.g., socioeconomic status, education level, and race/ethnicity, are a major cause for the disparities observed in the care of chronic disease. Lack of access and delay in receiving care result in worse outcomes for patients from minorities and underserved populations. Those barriers to medical care complicate patients monitoring and continuity in treatment.

In the US, Minorities and low-income populations are less likely to access and receive preventive services necessary to detect conditions at an early stage.

The majority of US health care and economic costs associated with medical conditions are for the costs of chronic diseases and conditions and associated health risk behaviors. Eighty-four percent of all health care spending in 2006 was for the 50% of the population who have one or more chronic medical conditions (CDC, 2014).

People with British Gulf War syndrome who used personal organophosphate pesticides may be more likely to report the symptoms of MCS.

RLS symptoms may gradually worsen with age, though more slowly for those with the idiopathic form of RLS than for patients who also have associated medical condition. Nevertheless, current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some patients have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear. Being diagnosed with RLS does not indicate or foreshadow another neurological disease.

A functional disorder is a medical condition that impairs the normal function of a bodily process, but where every part of the body looks completely normal under examination, dissection or even under a microscope. This stands in contrast to a structural disorder (in which some part of the body can be seen to be abnormal) or a psychosomatic disorder (in which symptoms are caused by psychological or psychiatric illness). Definitions vary somewhat between fields of medicine.

Generally, the mechanism that causes a functional disorder is unknown, poorly understood, or occasionally unimportant for treatment purposes. The brain or nerves are often believed to be involved. It is common that a person with one functional disorder will have others.

RLS affects an estimated 2.5–15% of the American population. A minority (around 2.7% of the population) experience daily or severe symptoms. RLS is twice as common in women as in men, and Caucasians are more prone to RLS than people of African descent. RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern region, and in 1–5% of those from the Far East, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome.

With age, RLS becomes more common, and RLS diagnosed at an older age runs a more severe course.

RLS is even more common in individuals with iron deficiency, pregnancy, or end-stage kidney disease. Poor general health is also linked.

Neurologic conditions linked to RLS include Parkinson's disease, spinal cerebellar atrophy, spinal stenosis, lumbosacral radiculopathy and Charcot–Marie–Tooth disease type 2. Approximately 80–90% of people with RLS also have periodic limb movement disorder (PLMD), which causes slow "jerks" or flexions of the affected body part. These occur during sleep (PLMS = periodic limb movement while sleeping) or while awake (PLMW—periodic limb movement while waking).

The National Sleep Foundation's 1998 "Sleep in America" poll showed that up to 25 percent of pregnant women developed RLS during the third trimester.

A variety of inciting infections have been observed. The most common infection sites are in the upper respiratory tract: including rhinitis, sinusitis, and pharyngitis. The specific microbe most commonly recognized has been group A Streptococcus. Mycoplasma pneumonia, influenza, and other common viruses have also been noted. Influenza has often been well-documented anecdotally at both initial onset and exacerbations of PANS.

A number of additional infections, including gastrointestinal infections, dental infection, herpes simplex, varicella, Epstein-Barr virus, enterovirus, Kawasaki disease, and anaphylactoid purpura, have been mentioned to be associated with the onset or exacerbation of PANS symptoms in a small number of cases.

The causes of pain children are similar to causes of pain in adults.

Pain can be experienced in many ways and is dependent upon the following factors in each child:

- prior painful episodes or treatments

- age and developmental stage

- disease or type of trauma

- personality

- culture

- socioeconomic status

- presence of family members and family dynamics.

Cancer pain is managed differently in children. Clinicians treating cancer pain can come from a variety of disciplines or specialties. Typically, medical history, physical examinations, age and overall health of the child is evaluated. The type of cancer may influence decisions about pain management. The extent of the cancer, the tolerance of the child to specific medications, procedure or therapies is also taken into account. The preferences of the parent or caregiver contribute to the determining of the best way to treat cancer pain. For cancer pain, opioids are helpful and can be taken orally. The side effects are: constipation, fatigue, and disorientation. Others are given IV, subcutaneous, or trans-dermal. Switching medications may be necessary at times. Dosing for children is based upon studies with adults or short-term studies. Children can develop opioid tolerance where larger doses are needed to have the same effect. When resistance to opioids develop, the pain responsiveness is reset and pain increases. Tolerance is likely to develop in younger children.

Whether a given medical condition is termed a "functional disorder" depends in part on the state of knowledge. Some diseases, including epilepsy, schizophrenia, and migraine headaches were once considered functional disorders, but are no longer generally classified that way.

At the time of first PANS presentation, note any family history of pharyngitis, impetigo, perianal dermatitis, and GAS infections. If possible, family members should have a throat swab cultured for GAS. Ongoing vigilance against GAS infections in any of the patient’s close contacts is important, as symptom exacerbations have been reported following exposure to a sibling with GAS (even when the PANDAS patient had no evidence of infection). Prompt medical attention to symptoms suggestive of streptococcal infection is important not only to protect the patient, but also siblings, who may be at an increased genetic risk for PANS.

A growing body of evidence supports that prevention is effective in reducing the effect of chronic conditions; in particular, early detection results in less severe outcomes. Clinical preventive services include screening for the existence of the disease or predisposition to its development, counseling and immunizations against infectious agents. Despite their effectiveness, the utilization of preventive services is typically lower than for regular medical services. In contrast to their apparent cost in time and money, the benefits of preventive services are not directly perceived by patient because their effects are on the long term or might be greater for society as a whole than at the individual level.

Therefore, public health programs are important in educating the public, and promoting healthy lifestyles and awareness about chronic diseases. While those programs can benefit from funding at different levels (state, federal, private) their implementation is mostly in charge of local agencies and community-based organizations.

Studies have shown that public health programs are effective in reducing mortality rates associated to cardiovascular disease, diabetes and cancer, but the results are somewhat heterogeneous depending on the type of condition and the type of programs involved. For example, results from different approaches in cancer prevention and screening depended highly on the type of cancer.

The rising number of patient with chronic diseases has renewed the interest in prevention and its potential role in helping control costs. In 2008, the Trust for America's Health produced a report that estimated investing $10 per person annually in community-based programs of proven effectiveness and promoting healthy lifestyle (increase in physical activity, healthier diet and preventing tobacco use) could save more than $16 billion annually within a period of just five years.

Magnesium deficiency causes neurogenic inflammation in a rat model. Researchers have theorized that since substance P which appears at day five of induced magnesium deficiency, is known to stimulate in turn the production of other inflammatory cytokines including IL-1, Interleukin 6 (IL-6), and TNF-alpha (TNFα), which begin a sharp rise at day 12, substance P is a key in the path from magnesium deficiency to the subsequent cascade of neuro-inflammation. In a later study, researchers provided rats dietary levels of magnesium that were reduced but still within the range of dietary intake found in the human population, and observed an increase in substance P, TNF alpha (TNFα) and Interleukin-1 beta (IL-1β), followed by exacerbated bone loss. These and other data suggest that deficient dietary magnesium intake, even at levels not uncommon in humans, may trigger neurogenic inflammation and lead to an increased risk of osteoporosis.

Pain is the main reason for visiting an emergency department in more than 50% of cases, and is present in 30% of family practice visits. Several epidemiological studies have reported widely varying prevalence rates for chronic pain, ranging from 12 to 80% of the population. It becomes more common as people approach death. A study of 4,703 patients found that 26% had pain in the last two years of life, increasing to 46% in the last month.

A survey of 6,636 children (0–18 years of age) found that, of the 5,424 respondents, 54% had experienced pain in the preceding three months. A quarter reported having experienced recurrent or continuous pain for three months or more, and a third of these reported frequent and intense pain. The intensity of chronic pain was higher for girls, and girls' reports of chronic pain increased markedly between ages 12 and 14.

There are established epigenetic and environmental risk factors for RA. Smoking is an established risk factor for RA in Caucasian populations, increasing the risk three times compared to non-smokers, particularly in men, heavy smokers, and those who are rheumatoid factor positive. Modest alcohol consumption may be protective.

Silica exposure has been linked to RA.

RA reduces lifespan on average from three to twelve years. According to the UK's National Rheumatoid Arthritis Society, Young age at onset, long disease duration, the concurrent presence of other health problems (called co-morbidity), and characteristics of severe RA—such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints—have been shown to associate with higher mortality". Positive responses to treatment may indicate a better prognosis. A 2005 study by the Mayo Clinic noted that RA sufferers suffer a doubled risk of heart disease, independent of other risk factors such as diabetes, alcohol abuse, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor. It is possible that the use of new biologic drug therapies extend the lifespan of people with RA and reduce the risk and progression of atherosclerosis. This is based on cohort and registry studies, and still remains hypothetical. It is still uncertain whether biologics improve vascular function in RA or not. There was an increase in total cholesterol and HDLc levels and no improvement of the atherogenic index.

Pain is a distressing feeling often caused by intense or damaging stimuli. Because it is a complex, subjective phenomenon, defining pain has been a challenge. The International Association for the Study of Pain's widely used definition states: "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." In medical diagnosis, pain is regarded as a symptom of an underlying condition.

Pain motivates the individual to withdraw from damaging situations, to protect a damaged body part while it heals, and to avoid similar experiences in the future. Most pain resolves once the noxious stimulus is removed and the body has healed, but it may persist despite removal of the stimulus and apparent healing of the body. Sometimes pain arises in the absence of any detectable stimulus, damage or disease.

Pain is the most common reason for physician consultation in most developed countries. It is a major symptom in many medical conditions, and can interfere with a person's quality of life and general functioning. Simple pain medications are useful in 20% to 70% of cases. Psychological factors such as social support, hypnotic suggestion, excitement, or distraction can significantly affect pain's intensity or unpleasantness. In some arguments put forth in physician-assisted suicide or euthanasia debates, pain has been used as an argument to permit people who are terminally ill to end their lives.